FaCD Online Syndrome Fact Sheet

Last updated: 11 May 2009

Name: Ataxia Telangiectasia

Synonym: AT, Louis-Bar syndrome

Mode of Inheritance: AR

OMIM number: 208900  


ATM, mapped to 11q22.3

Tumor features

breast cancer
colon cancer
gastric cancer
glioma of the brain
hepatocellular cancer (hepatoma)
histiocytosis (reticuloendotheliosis), malignant
Hodgkin disease (Hodgkin's lymphoma)
laryngeal cancer
leukemia, acute lymphoblastic (ALL)
leukemia, chronic lymphocytic (CLL)
non-Hodgkin lymphoma
ovarian cancer (i.e. epithelial origin)
parotid gland cancer
skin cancer, basal cell
skin cancer, squamous cell
thyroid cancer

Tumor features (possible)

leiomyosarcoma of the uterus
ovarian dysgerminoma
ovarian fibroma
ovarian gonadoblastoma
uterine leiomyoma

Non-tumor features

café au lait spots
cerebellar ataxia
growth deficieny
increased chromosomal breakage
increased/persistent serum AFP
ionizing radiation sensitivity, increased
mutagen sensitivity, increased
oculocutaneous telangiectasia
thymus hypoplasia/aplasia


Progressive ataxia usually develops during infancy. Telangiectasia occurs usually first in the bulbar conjunctivae and later over the bridge of the nose, auricles and other areas. Growth deficiency commonly presents itself during late infancy/childhood. Mental deficiency is a feature in about half of the cases.[1] Neoplasms develop in approximately 10 percent of patients, especially lymphoid tumors. Many patients do not survive to adulthood, lung infections and neurological complications being the main cause of death. Non-Hodgkin lymphoma (mostly of the histological subtype associated with 14q translocations), acute lymphoblastic leukemia and Hodgkin disease (mostly of lymphocytic depletion type) are the most frequent neoplasms in AT patients[2]. Myeloid tumors are absent[3]. The increase in lymphoid malignancy is caused by both B- and T-cell tumors[3;4]. T-cell tumors may develop at any age and may be T-ALL, T-cell lymphoma or T-cell prolymphocytic leukemia[3]. The recognition of lymphomas may be delayed due to confusion with known infectious complications in AT[5]. A wide range of other neoplasms have been reported, including gastric cancer, colon cancer, chronic lymphoblastic leukemia, brain tumors, craniopharyngioma, liver cancer, laryngeal cancer, leiomyoma and leiomyosarcoma of the uterus, dysgerminoma, fibroadenoma and gonadoblastoma of the ovaries, testicular seminoma and basal cell and squamous cell skin cancer [5-13].

Inheriting one mutated copy of the AT gene (ATM) increases breast cancer risk in females, and may turn out to contribute significantly to the total breast cancer burden. However, data are inconclusive as to the magnitude of this contribution and strength of this risk factor[14-25]. Overall, there appears to be a twofold increase in breast cancer risk for ATM mutation carriers[36]. Byrnes et al argue that in families with a strong history of breast cancer this relative risk implies a rather high absolute risk[37]. Broeks et al.[26] found the relatively high percentage of 8.5 % ATM mutation carriers in a group of 82 breast cancer patients selected for early onset (<45 years), long-term survival and bilaterality. Baynes et al showed that is unlikely that common ATM variants increase breast cancer risk[27]. Johnson et al confirmed this and argued that it is rather a combination of variants in different genes (ATM, BRCA1, BRCA2) that confers an increased breast cancer risk[28]. Common ATM alleles have been suggeted to decrease rather than increase contralateral breast cancer risk[34]. Single rare ATM allels may still confer a substantially increased breast cancer risk[29]. Missense ATM mutations do not appear to increase total cancer risk or breast cancer risk[35]. Balleine et al reported that breast cancer occurring in carriers of ATM variants is not associated with distinctive histopathological features[30].

Fibroblast cultures of AT heterozygotes show increased radiosensitivity and given the fact that breast cancer is a well known complication to occur in long-term survivors of Hodgkin disease who received mantle-field irradiation, it has been questioned whether germline mutations in ATM contributed to this increase of breast cancer risk. Studies by Broeks et al.[31] and Nichols et al.[32] did not support a major contribution of germline ATM mutations to the breast cancer risk in these type of patients. The same was true for contralateral breast cancer risk after radiation therapy for the first breast tumor, as reported by Shafman et al.[33].


A-T Children's Project 18 1 08
Ataxia-Telangiectasia Society
Ataxia-TelangiectasiaMutation Database 18 1 08


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[11] Weinstein S, Scottolini AG, Loo SYT, Caldwell PC, Bhagavan NV. Ataxia telangiectasia with hepatocellular carcinoma in a 15-year-old girl and studies of her kindred. Arch Pathol Lab Med 1985; 109:1000-1004.
[12] Koksal Y, Caliskan U, Ucar C, Yurtcu M, Artac H, Ilerisoy-Yakut Z, Reisli I. Dysgerminoma in a child with ataxia-telangiectasia. Pediatric hematology and oncology 2007; 24(6):431-6.
[13] Masri AT, Bakri FG, Al-Hadidy AM, Musharbash AF, Al-Hussaini M. Ataxia-telangiectasia complicated by craniopharyngioma--a new observation. Pediatric neurology 2006; 35(4):287-8.
[14] Swift M, Morrell D, Massey RB, Chase CL. Incidence of cancer in 161 families affected by ataxia-teleangiectasia. N Engl J Med 1991; 325:1831-1836.
[15] Easton DF. Cancer risks in A-T heterozygotes. Int J Radiat Biol 1994; 66(6):S177-S182.
[16] Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tahle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R. A single Ataxia Teleangiectasia gene with a product similar to PI-3 kinase. Science 1995; 268:1749-1753.
[17] Nowak R. Discovery of AT gene sparks biomedical bonanza. Science 1995; 268:1700-1701.
[18] Vorechovsky I, Luo LP, Lindblom A, Negrini M, Webster ADB, Croce CM, Hammarstrom L. ATM mutations in cancer families. Cancer Res 56[18], 4130-4133. 1996.
[19] Vorechovsky I, Rasio D, Luo LP, Monaco C, Hammarstrom L, Webster ADB, Zaloudik J, Barbanti-Brodano G, James M, Russo G, Croce CM, Negrini M. The ATM gene and susceptibility to breast cancer: Analysis of 38 breast tumors reveals no evidence for mutation. Cancer Res 56[12], 2726-2732. 1996.
[20] Athma P, Rappaport R, Swift M. Molecular genotyping shows that ataxia-telangiectasia heterozygotes are predisposed to breast cancer. Cancer Genet Cytogenet 92[2], 130-134. 1996.
[21] Fitzgerald MG, Bean JM, Hegde SR, Unsal H, Macdonald DJ, Harkin DP, Finkelstein DM, Isselbacher KJ, Haber DA. Heterozygous ATM mutations do not contribute to early onset of breast cancer. Nat Genet 15[3], 307-310. 1997.
[22] Bishop DT, Hopper J. AT-tributable risks? Nat Genet 1997; 15:226.
[23] Chen JD, Giesler G, Birkholtz G, Lindblom P, Rubio C, Lindblom A. The role of ataxia-telangiectasia heterozygotes in familial breast cancer. Cancer Res 58[7], 1376-1379. 1998.
[24] Swift M, Chase CL, Morell D. Cancer predisposition of ataxia-telangiectasia heterozygotes. Cancer Genet Cytogenet 1990; 46:21-27.
[25] Janin N, Andrieu N, Ossian K, Lauge A, Croquette MF, Griscelli C, Debre M, Bressac-de Paillerets B, Aurias A, Stoppa-Lyonnet D. Breast cancer risk in ataxia telangiectasia (AT) heterozygotes: haplotype study in french AT families. Br J Cancer 80[7], 1042-1045. 1999.
[26] Broeks A, Urbanus JHM, Floore AN, Dahler EC, Klijn JGM, Rutgers EJTh, Devilee P, Russell NS, van Leeuwen FE, van't Veer LJ. ATM-heterozygous germline mutations contribute to breast cancer- susceptibility. Am J Hum Genet 2000; 66(2):494-500.
[27] Baynes C, Healey CS, Pooley KA, Scollen S, Luben RN, Thompson DJ, Pharoah PD, Easton DF, Ponder BA, Dunning AM, . Common variants in the ATM, BRCA1, BRCA2, CHEK2 and TP53 cancer susceptibility genes are unlikely to increase breast cancer risk. Breast cancer research : BCR 2007; 9(2):R27.
[28] Johnson N, Fletcher O, Palles C, Rudd M, Webb E, Sellick G, dos Santos Silva I, McCormack V, Gibson L, Fraser A, Leonard A, Gilham C, Tavtigian SV, Ashworth A, Houlston R, Peto J. Counting potentially functional variants in BRCA1, BRCA2 and ATM predicts breast cancer susceptibility. Human molecular genetics 2007; 16(9):1051-7.
[29] Bernstein JL, Teraoka S, Southey MC, Jenkins MA, Andrulis IL, Knight JA, John EM, Lapinski R, Wolitzer AL, Whittemore AS, West D, Seminara D, Olson ER, Spurdle AB, Chenevix-Trench G, Giles GG, Hopper JL, Concannon P. Population-based estimates of breast cancer risks associated with ATM gene variants c.7271T>G and c.1066-6T>G (IVS10-6T>G) from the Breast Cancer Family Registry. Human mutation 2006; 27(11):1122-8.
[30] Balleine RL, Murali R, Bilous AM, Farshid G, Waring P, Provan P, Byth K, Thorne H, , Kirk JA. Histopathological features of breast cancer in carriers of ATM gene variants. Histopathology 2006; 49(5):523-32.
[31] Broeks A, Russell NS, Floore AN, Urbanus JH, Dahler EC, van't Veer MB, Hagenbeek A, Noordijk EM, Crommelin MA, van Leeuwen FE, van't Veer LJ. Increased risk of breast cancer following irradiation for Hodgkin's disease is not a result of ATM germline mutations. Int J Radiat Biol 2000; 76(5):693-698.
[32] Nichols KE, Levitz S, Shannon KE, Wahrer DCR, Bell DW, Chang G, Hegde S, Neuberg D, Shafman T, Tarbell NJ, Mauch P, Ishioka C, Haber DA, Diller L. Heterozygous germline ATM mutations do not contribute to radiation-associated malignancies after Hodgkin's disease. J Clin Oncol 1999; 17(4):1259.
[33] Shafman TD, Levitz S, Nixon AJ, Gibans LA, Nichols KE, Bell DW, Ishioka C, Isselbacher KJ, Gelman R, Garber J, Harris JR, Haber DA. Prevalence of germline truncating mutations in ATM in women with a second breast cancer after radiation therapy for a contralateral tumor. Gene Chrom Cancer 2000; 27(2):124-129.
[34] Concannon P, Haile RW, Børresen-Dale AL, Rosenstein BS, Gatti RA, Teraoka SN, Diep TA, Jansen L, Atencio DP, Langholz B, Capanu M, Liang X, Begg CB, Thomas DC, Bernstein L, Olsen JH, Malone KE, Lynch CF, Anton-Culver H, Bernstein JL; Women's Environment, Cancer, and Radiation Epidemiology Study Collaborative Group. Variants in the ATM gene associated with a reduced risk of contralateral breast cancer.Cancer Res. 2008 Aug 15;68(16):6486-91.
[35] Dombernowsky SL, Weischer M, Allin KH, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG. Risk of cancer by ATM missense mutations in the general population.J Clin Oncol. 2008 Jun 20;26(18):3057-62.
[36] Ahmed M, Rahman N. ATM and breast cancer susceptibility.Oncogene. 2006 Sep 25;25(43):5906-11.
[37] Byrnes GB, Southey MC, Hopper JL. Are the so-called low penetrance breast cancer genes, ATM, BRIP1, PALB2 and CHEK2, high risk for women with strong family histories? Breast Cancer Res. 2008;10(3):208. Epub 2008 Jun 5.